Global patent index - EP 1082336 A2

EP 1082336 A2 2001-03-14 - APOPTOSIS MODULATORS THAT INTERACT WITH THE HUNTINGTON'S DISEASE GENE

Title (en)

APOPTOSIS MODULATORS THAT INTERACT WITH THE HUNTINGTON'S DISEASE GENE

Title (de)

APOPTOSEMODULATOREN, DIE MIT DEM GEN DER HUNTINGTONSCHEN KRANKHEIT REAGIEREN

Title (fr)

MODULATEURS D'APOPTOSE INTERAGISSANT AVEC LE GENE DE LA MALADIE DE HUNTINGTON

Publication

EP 1082336 A2 (EN)

Application

EP 99925933 A

Priority

  • US 9911743 W
  • US 8519998 A

Abstract (en)

[origin: WO9960986A2] A family of proteins, including a specific human protein designated as HIP1, has been identified that interact differently with the gene product of a normal (16 CAG repeat) and an expanded (>44 CAG repeat) HD gene. Expression of the HIP1 protein was found to be enriched in the brain. Analysis of the sequence of the HIP1 protein indicated that it includes a death effector domain (DED), suggesting an apoptotic function. Thus, it appears that a normal function of Huntingtin may be to bind HIP1 and related apoptosis modulators, reducing its effectiveness in stimulating cell death. Since expanded huntingtin performs this function less well, there is an increase in HIP1-modulated cell death in individuals with an expanded repeat in the HD gene. This understanding of the likely role of huntingtin and HIP1 or related proteins (collectively "HIP-apoptosis modulating proteins") in the pathology of Huntington's disease offers several possibilities for therapy. First, because the function of huntingtin apparently depends at least in part on the ability to interact with HIP-apoptosis modulating proteins, added expression (e.g., via gene therapy) of normal (non-expanded) huntingtin or of the HIP-binding region of huntingtin should provide a therapeutic benefit. Other DED-interacting peptides could also be used to mask and reduce the interaction of HIP-apoptosis modulating proteins with the death signaling complex. Alternatively, a mutant form of HIP-protein from which the DED has been deleted might be introduced, for example using gene therapy techniques. Because HIP-apoptosis modulating proteins have been shown to self-associate, a protein with a deleted DED may compete with endogenous HIP-protein in the formation of these associations, thereby reducing the amount of apoptotically-active HIP-protein.

IPC 1-7 (main, further and additional classification)

C07H 21/04; C07K 5/00; C07K 14/47; C12N 15/12; C12Q 1/68

IPC 8 full level (invention and additional information)

C12N 15/09 (2006.01); A61K 31/711 (2006.01); A61K 45/00 (2006.01); A61K 48/00 (2006.01); A61P 43/00 (2006.01); C07K 14/47 (2006.01); C07K 16/18 (2006.01); C12Q 1/68 (2006.01); A61K 38/00 (2006.01)

CPC (invention and additional information)

C07K 16/18 (2013.01); C07K 14/47 (2013.01); C07K 14/4747 (2013.01); A61K 38/00 (2013.01)

Designated contracting state (EPC)

AT BE CH DE DK ES FI FR GB GR IE IT LI LU NL PT SE

EPO simple patent family

WO 9960986 A2 19991202; WO 9960986 A3 20000420; AU 4212199 A 19991213; CA 2329249 A1 19991202; EP 1082336 A2 20010314; EP 1082336 A4 20050119; JP 2002516075 A 20020604; US 6235879 B1 20010522

INPADOC legal status

2005-04-06 [18W] WITHDRAWN

- Ref Legal Event Code: 18W

- Effective date: 20050208

2005-01-19 [A4] SUPPLEMENTARY SEARCH REPORT

- Ref Legal Event Code: A4

- Effective date: 20041208

2005-01-19 [RIC1] CLASSIFICATION (CORRECTION)

- Ref Legal Event Code: RIC1

- IPC: 7C 07H 21/04 A

2005-01-19 [RIC1] CLASSIFICATION (CORRECTION)

- Ref Legal Event Code: RIC1

- IPC: 7C 12Q 1/68 B

2005-01-19 [RIC1] CLASSIFICATION (CORRECTION)

- Ref Legal Event Code: RIC1

- IPC: 7C 07K 5/00 B

2005-01-19 [RIC1] CLASSIFICATION (CORRECTION)

- Ref Legal Event Code: RIC1

- IPC: 7C 07K 14/47 B

2005-01-19 [RIC1] CLASSIFICATION (CORRECTION)

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- IPC: 7C 12N 15/12 B

2001-03-14 [17P] REQUEST FOR EXAMINATION FILED

- Ref Legal Event Code: 17P

- Effective date: 20001227

2001-03-14 [AK] DESIGNATED CONTRACTING STATES:

- Ref Legal Event Code: AK

- Designated State(s): AT BE CH DE DK ES FI FR GB GR IE IT LI LU NL PT SE